O-Glycosylation of Serum IgD in IgA Nephropathy

Identification of Distinct Glycoforms of IgA1 in Plasma from Patients with Immunoglobulin A (IgA) Nephropathy and Healthy Individuals

“…Overall our results are consistent with several historical studies that have detected the presence of IgA1 containing the Tn antigen in plasma of both IgAN patients and control individuals in their published data (42,45,46,48,56,58,60). Several studies have also reported minimal or even no differences between galactosylation of IgA1 from IgAN patients and IgA1 from control donors, showing in their data similar reactivity with lectins (HAA, HPA or VVA) specific to galactose-deficient O-glycans (48,60,61).…”

“…Several studies have also reported minimal or even no differences between galactosylation of IgA1 from IgAN patients and IgA1 from control donors, showing in their data similar reactivity with lectins (HAA, HPA or VVA) specific to galactose-deficient O-glycans (48,60,61). Yet, the conclusions of many of these reports identify galactose-deficient IgA1 as a hallmark of IgAN and as a marker to discriminate between IgAN patients and healthy individuals.…”

O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy

“…At present, little is known about the control of IgA1 O-glycosylation in B lymphocytes and plasma cells. We recently showed no undergalactosylation of serum IgD in IgAN, arguing that the O-glycosylation defect is not generic in B lineage cells in IgAN but arises only after class switching to IgA (15). Taken with other published data, this finding suggests a defect in IgA-committed B cells after antigen encounter.…”

“…However, altered IgA1 O-galactosylation cannot be attributed fully to a straightforward lack of galactosylating activity in affected individuals. Any defect must be restricted to IgA1-producing B cells or subpopulations thereof, because other O-glycosylated proteins such as C1 inhibitor (22) and IgD (15) do not share the under-O-galactosylation of IgA1.…”

“…It is plausible that the IgA1 O-glycoforms produced may change during the development of immune responses. Some evidence for this is provided by our recent observation that the O-glycosylation patterns of serum IgD (restricted to primary immune responses) and IgA1 (mostly produced during secondary responses) are distinct from one another, despite that both of these Ig isotypes carry the same type of O-linked sugar chains (15). It therefore is possible that IgA1 with high VV binding is an indicator of a certain stage of development of an IgA response, which is overrepresented in IgAN.…”